FSH受体基因变异组合对卵巢刺激反应的叠加效应

IF 2.6 3区医学 Q2 OBSTETRICS & GYNECOLOGY

Reproductive Sciences Pub Date : 2024-11-01 Epub Date: 2024-09-25 DOI:10.1007/s43032-024-01700-x

Ana Raquel Neves, Sandra Garcia, Lan N Vuong, Christophe Blockeel, Claudia Spits, Nikolaos P Polyzos

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引用次数: 0

摘要

分析FSHR基因内的多态性组合是否会影响卵巢对刺激的反应（OR）。一项多中心前瞻性队列研究于2016年11月至2019年6月在欧洲和亚洲进行，研究对象包括38岁以下的预测正常反应者。患者在GnRH拮抗剂方案中使用固定剂量150 IU rFSH进行卵巢刺激。对 FSHR 变体 rs6165、rs6166 和 rs1394205 进行了基因分型，并将其组合成二联型。与其他二联型相比，rs6165/rs6166 基因型 AG/AG 表现出更多的低反应（33.1% 对 24%，adjOR 1.77 [95%CI 1.08-2.90]）和更低的卵泡对卵母细胞指数（FOI）（EMD -11.72 [95%CI -20.89;-2.55]）。基因型 GG/AA 的低反应率较低（19.1% vs. 31%，adjOR 0.48 [95%CI 0.24-0.96]），而 AA/AA 的 FOI 较高（EMD 20.04 [95%CI 4.51;35.56]）。关于 rs6165/rs1394205，基因型为 AG/AG 的卵母细胞较少（EMD -1.99 [95%CI -3.57;-0.42]），FOI 较低（EMD -12.07 [95%CI -23.09;-1.05]），而基因型为 AA/AG 的 FORT 较高（EMD 17.88 [95%CI 3.77;31.98]）。关于 rs6166/rs1394205，发现基因型 AA/GG 的低反应率较低（16.3% vs. 29.5%，adjOR 0.42 [95%CI 0.19-0.97]），卵母细胞较多（EMD 3.45 [95%CI 1.57;5.34]），FOI 较高（EMD 17.57 [95%CI 4.41;30.73）。基因型为 AA/AG 的患者 FORT 较高（EMD 13.47 [95%CI 2.51,24.42]），而基因型为 AG/AA 的患者反应较低（56.3% vs. 26.4%，adjOR 6.30 [95%CI 1.88;21.08]），FOI 较低（EMD -23.51 [95%CI -45.04;-1.97]）。与我们之前的研究一致，FSHR 多态性对 OR 有显著的统计学影响，无论是单独影响还是相关影响。然而，只有rs6166/rs1394205基因型AA/GG似乎对临床有显著影响，它降低了低反应的发生率，提高了卵母细胞产量，增加了FOI。

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The Additive Effect of Combinations of FSH Receptor Gene Variants in Ovarian Response to Stimulation.

To analyze whether combinations of polymorphisms within FSHR gene influence ovarian response (OR) to stimulation. A multicenter prospective cohort study was conducted from 11/2016-06/2019 in Europe and Asia including predicted normo-responders under 38y. Patients underwent ovarian stimulation using fixed-dose 150 IU rFSH in a GnRH antagonist protocol. FSHR variants rs6165, rs6166 and rs1394205 were genotyped and combined in diplotypes. OR was compared following multivariable regression. rs6165/rs6166 genotype AG/AG exhibited more hypo-response (33.1% vs. 24%,adjOR 1.77 [95%CI 1.08-2.90]) and lower Follicle to Oocyte Index (FOI) compared with other diplotypes (EMD -11.72 [95%CI -20.89;-2.55]). Genotype GG/AA showed less hypo-response (19.1% vs. 31%, adjOR 0.48 [95%CI 0.24-0.96]), while AA/AA had higher FOI (EMD 20.04 [95%CI 4.51;35.56]). Concerning rs6165/rs1394205, less oocytes (EMD -1.99 [95%CI -3.57;-0.42]) and lower FOI (EMD -12.07 [95%CI -23.09;-1.05]) were retrieved with genotype AG/AG and higher FORT with genotype AA/AG (EMD 17.88 [95%CI 3.77;31.98]). Regarding rs6166/rs1394205, less hypo-response (16.3% vs. 29.5%,adjOR 0.42 [95%CI 0.19-0.97]), more oocytes (EMD 3.45 [95%CI 1.57;5.34]) and higher FOI (EMD 17.57 [95%CI 4.41;30.73) were found with genotype AA/GG. Genotype AA/AG presented higher FORT (EMD 13.47 [95%CI 2.51,24.42]), while more hypo-response (56.3% vs. 26.4%,adjOR 6.30 [95%CI 1.88;21.08]) and lower FOI (EMD -23.51 [95%CI -45.04;-1.97]) was reported with AG/AA. In accordance with our previous studies, FSHR polymorphisms have a statistically significant impact on OR, both individually and in association. However, only rs6166/rs1394205 genotype AA/GG seems to have a clinically significant effect, with a decrease in the prevalence of hypo-response, higher oocyte yield and increase in FOI.

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来源期刊

Reproductive Sciences 医学-妇产科学

CiteScore

5.50

自引率

3.40%

发文量

322

审稿时长

4-8 weeks

期刊介绍： Reproductive Sciences (RS) is a peer-reviewed, monthly journal publishing original research and reviews in obstetrics and gynecology. RS is multi-disciplinary and includes research in basic reproductive biology and medicine, maternal-fetal medicine, obstetrics, gynecology, reproductive endocrinology, urogynecology, fertility/infertility, embryology, gynecologic/reproductive oncology, developmental biology, stem cell research, molecular/cellular biology and other related fields.